ALG8

id: Q9BVK2
gene_symbol: ALG8
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ALG8 is the endoplasmic reticulum (ER)-lumenal, Dol-P-Glc-dependent
  alpha-1,3-glucosyltransferase (EC 2.4.1.265) that catalyzes the second of the
  three glucosylation steps in assembly of the dolichol-linked oligosaccharide
  (LLO), the Glc3Man9GlcNAc2 glycan precursor used for protein N-linked
  glycosylation. Acting on the lumenal face of the ER membrane, it transfers a
  glucose residue from dolichyl-phosphate-glucose (Dol-P-Glc, not UDP-Glc) onto
  the lipid-linked intermediate Glc1Man9GlcNAc2-PP-dolichol to give
  Glc2Man9GlcNAc2-PP-dolichol, the substrate for the following enzyme ALG10.
  ALG8 is a polytopic (multi-pass) ER membrane protein of the ALG6/ALG8
  glucosyltransferase family (CAZy GT57). It functions in the dolichol-linked
  oligosaccharide biosynthetic process and, downstream, in protein N-linked
  glycosylation. Loss-of-function variants cause the autosomal recessive
  multisystem congenital disorder of glycosylation type Ih (ALG8-CDG / CDG-Ih),
  characterized by hypoglycosylation of serum glycoproteins; ALG8 variants are
  also associated with isolated polycystic liver disease.
alternative_products:
- name: '1'
  id: Q9BVK2-1
- name: '2'
  id: Q9BVK2-2
  sequence_note: VSP_046291
existing_annotations:
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      ALG8 is an ER membrane enzyme; the phylogenetically inferred ER membrane
      localization is fully consistent with experimental and UniProt evidence.
      ALG8 is a multi-pass ER membrane protein that acts on the lumenal side of
      the ER membrane during LLO assembly. Correct and core.
    action: ACCEPT
    reason: >-
      IBA localization to the ER membrane matches the UniProt-curated
      subcellular location and the enzyme's role in ER-lumenal LLO assembly.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "Multi-pass membrane protein"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      ALG8 adds the second glucose to the growing lipid-linked oligosaccharide
      (LLO), a defining step of dolichol-linked oligosaccharide biosynthesis.
      This is the core biological process for the gene and is supported by
      experimental (IMP) evidence in humans as well as the phylogenetic
      inference. Correct and core.
    action: ACCEPT
    reason: >-
      The gene's characterized enzymatic step (adding glucose to
      Glc1Man9GlcNAc2-PP-Dol) is part of dolichol-linked oligosaccharide
      biosynthesis; the IBA agrees with experimental annotations from
      PubMed:12480927 and PubMed:15235028.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
- term:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      This is the precise, correct molecular function of ALG8: the
      Dol-P-Glc-dependent alpha-1,3-glucosyltransferase (EC 2.4.1.265) that adds
      the second glucose from Dol-P-Glc onto Glc1Man9GlcNAc2-PP-Dol to give
      Glc2Man9GlcNAc2-PP-Dol. The phylogenetic inference agrees with human
      experimental evidence and is the core enzymatic activity.
    action: ACCEPT
    reason: >-
      This IBA term is the exact characterized activity of ALG8 and matches the
      UniProt catalytic-activity annotation and the experimental IMP
      annotations. Core molecular function.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
      - reference_id: PMID:12480927
        supporting_text: "which catalyzes this reaction"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      IEA localization to the ER membrane derived from the UniProt
      Swiss-Prot subcellular location mapping. This agrees with the
      experimentally supported (PubMed:15235028) UniProt subcellular location
      annotation. Correct.
    action: ACCEPT
    reason: >-
      The mapping reproduces the curated ER membrane location, which is
      experimentally grounded.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0016758
    label: hexosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO mapping (IPR004856, ALG6/ALG8 glucosyltransferase family) to
      the generic parent term hexosyltransferase activity. This is correct but
      much more general than ALG8's characterized activity (GO:0042283,
      dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase
      activity), which is already annotated.
    action: MODIFY
    reason: >-
      Not wrong, but too general given the specific EC 2.4.1.265 activity is
      established. Replace with the specific glucosyltransferase term already
      supported by experimental and phylogenetic evidence.
    proposed_replacement_terms:
      - id: GO:0042283
        label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "Belongs to the ALG6/ALG8 glucosyltransferase family"
- term:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Automated (RHEA:31307 / EC:2.4.1.265) assignment of the precise enzymatic
      activity. This matches the UniProt catalytic activity annotation and the
      experimental evidence. Correct and core.
    action: ACCEPT
    reason: >-
      RHEA/EC-based IEA reproduces the exact experimentally established activity
      (EC 2.4.1.265), consistent with the IBA and IMP annotations to the same
      term.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPI from a large-scale interactome/edgotyping study
      (Sahni et al. 2015). The recorded interactor is CREB3 (UniProtKB:O43889-2).
      This uninformative MF term does not describe ALG8's actual glucosyltransferase
      function and the interaction has no established biological role for ALG8.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" (GO:0005515) is uninformative and comes from a
      high-throughput screen; it is retained but flagged as over-annotation
      rather than removed, per curation policy for experimental IPIs.
    supported_by:
      - reference_id: PMID:25910212
        supporting_text: "two-thirds of disease-associated alleles perturb protein-protein"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "Q9BVK2; O43889-2: CREB3; NbExp=3; IntAct=EBI-3921603, EBI-625022;"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPI from the HuRI human binary (Y2H) interactome
      map (Luck et al. 2020). Recorded interactors for ALG8 include CYB5R3
      (P00387), CLRN1 (P58418), BIK (Q13323), FAM209A (Q5JX71), MFSD6 (Q6ZSS7),
      GPX8 (Q8TED1), CREB3L1 (Q96BA8) and SAR1A (Q9NR31). These are largely
      other ER/membrane proteins; none establishes a specific molecular
      function for ALG8, and the term itself is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      "Protein binding" is uninformative and derives from a proteome-scale Y2H
      screen; retained but flagged as over-annotation per policy for
      experimental IPIs.
    supported_by:
      - reference_id: PMID:32296183
        supporting_text: "reference interactome map of human binary protein interactions"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "Q9BVK2; P00387: CYB5R3; NbExp=3; IntAct=EBI-3921603, EBI-1046040;"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      Bare "protein binding" IPI from the BioPlex 3.0 affinity-purification
      mass-spectrometry interactome (Huttlin et al. 2021). The recorded
      interactor is ALG6 (UniProtKB:Q9Y672), the alpha-1,3-glucosyltransferase
      that acts immediately before ALG8 in LLO assembly; a physical association
      between these two sequential ER-membrane glucosyltransferases is
      biologically plausible, but "protein binding" is still an uninformative
      MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Although the ALG6 interactor is pathway-relevant, GO:0005515 conveys no
      specific molecular function; retained but flagged as over-annotation per
      policy for experimental IPIs.
    supported_by:
      - reference_id: PMID:33961781
        supporting_text: "affinity-purification"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "Q9BVK2; Q9Y672: ALG6; NbExp=2; IntAct=EBI-3921603, EBI-11337956;"
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      IEA transfer from mouse ortholog (Q6P8H8) via Ensembl Compara to protein
      N-linked glycosylation. ALG8 builds the LLO glycan precursor that is
      transferred to nascent proteins, so involvement in N-linked glycosylation
      is correct, though it is one step removed from the direct enzymatic
      reaction (LLO assembly).
    action: ACCEPT
    reason: >-
      ALG8's role in assembling the Glc3Man9GlcNAc2 precursor makes it a
      genuine participant in protein N-linked glycosylation; consistent with
      experimental IMP and ISS annotations to the same term.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "the glycan precursors employed in\nCC       protein asparagine (N)-glycosylation"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446193
  qualifier: involved_in
  review:
    summary: >-
      Reactome TAS placing ALG8 in the LLO (dolichol lipid-linked
      oligosaccharide) biosynthesis and transfer pathway. This is the core
      biological process for ALG8 and is corroborated by experimental IMP
      annotations. Correct and core.
    action: ACCEPT
    reason: >-
      Reactome authored the LLO biosynthesis pathway including the ALG8-catalyzed
      second glucose addition; consistent with IBA/IMP annotations to the same
      term.
    supported_by:
      - reference_id: Reactome:R-HSA-446189
        supporting_text: "The second glucose (supplied from the donor dolichol-phosphate-glucose) is added to the N-glycan precursor, mediated by ALG8"
- term:
    id: GO:0098553
    label: lumenal side of endoplasmic reticulum membrane
  evidence_type: IC
  original_reference_id: PMID:15235028
  qualifier: is_active_in
  review:
    summary: >-
      Inferred by curator (IC) that ALG8 acts on the lumenal side of the ER
      membrane. The glucose additions occur after the LLO intermediate is
      flipped to the ER lumen, and ALG8 uses lumenal Dol-P-Glc; UniProt states
      the assembly "finishes in its lumen" and that ALG8 acts "In the lumen of
      the endoplasmic reticulum". This precise topological localization is
      correct and biologically informative.
    action: ACCEPT
    reason: >-
      The lumenal orientation of the ALG8-catalyzed glucosylation step is
      well established; the IC annotation captures the correct membrane
      topology and is consistent with UniProt.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
      - reference_id: PMID:15235028
        supporting_text: "(CDG-Ih) (ALG8 deficiency)"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IGI
  original_reference_id: PMID:15235028
  qualifier: is_active_in
  review:
    summary: >-
      Experimental (IGI, with yeast Alg8 P40351) support that human ALG8 is
      active in the ER membrane, from the CDG-Ih characterization study
      (Schollen et al. 2004). ALG8 is a multi-pass ER membrane enzyme; this is
      the core cellular location. Correct and core.
    action: ACCEPT
    reason: >-
      Genetic-interaction/complementation evidence (with the yeast ortholog)
      supports ER membrane activity; consistent with UniProt subcellular
      location. Curator read the full text of this abstract-only paper.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
      - reference_id: PMID:15235028
        supporting_text: "(CDG-Ih) (ALG8 deficiency)"
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IMP
  original_reference_id: PMID:15235028
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) evidence that ALG8 loss impairs protein N-linked
      glycosylation, from CDG-Ih patients with ALG8 deficiency who show
      under-glycosylated serum glycoproteins (Schollen et al. 2004). ALG8 builds
      the LLO precursor transferred to nascent proteins. Correct.
    action: ACCEPT
    reason: >-
      Patient-derived loss-of-function characterization demonstrates ALG8's
      requirement for normal N-glycosylation; the curator read the full text.
    supported_by:
      - reference_id: PMID:15235028
        supporting_text: "(CDG-Ih) (ALG8 deficiency)"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "the glycan precursors employed in\nCC       protein asparagine (N)-glycosylation"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:12480927
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) evidence from the founding CDG-Ih study (Chantret et
      al. 2003): patient fibroblasts with reduced ALG8 mRNA accumulate
      Man9GlcNAc2-PP-dolichol (and, with castanospermine, Glc1Man9GlcNAc2-PP-Dol),
      indicating inefficient addition of the second glucose to the LLO, and are
      rescued by wild-type ALG8 cDNA. This is the core biological process.
    action: ACCEPT
    reason: >-
      Loss-of-ALG8 blocks LLO maturation with accumulation of the immediate
      substrate, directly demonstrating involvement in dolichol-linked
      oligosaccharide biosynthesis. Core process.
    supported_by:
      - reference_id: PMID:12480927
        supporting_text: "suggesting inefficient addition of the second glucose residue onto"
      - reference_id: PMID:12480927
        supporting_text: "biosynthesis of the dolichyl-linked oligosaccharide"
- term:
    id: GO:0006488
    label: dolichol-linked oligosaccharide biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:15235028
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) evidence from a second CDG-Ih cohort (Schollen et al.
      2004): ALG8-deficient patients with characterized loss-of-function
      variants (T47P, G275D) show impaired LLO glucosylation. Confirms ALG8's
      role in dolichol-linked oligosaccharide biosynthesis. Core process.
    action: ACCEPT
    reason: >-
      Independent patient/variant characterization corroborates ALG8's
      requirement for LLO biosynthesis; curator read the full text.
    supported_by:
      - reference_id: PMID:15235028
        supporting_text: "(CDG-Ih) (ALG8 deficiency)"
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
- term:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:12480927
  qualifier: enables
  review:
    summary: >-
      Experimental (IMP) support for ALG8's Dol-P-Glc:Glc1Man9GlcNAc2-PP-dolichyl
      alpha-1,3-glucosyltransferase activity: Chantret et al. 2003 identify ALG8
      as the enzyme catalyzing addition of the second glucose to the LLO, with
      loss of function causing substrate accumulation and rescue by wild-type
      cDNA. Core molecular function.
    action: ACCEPT
    reason: >-
      Directly demonstrates the characterized enzymatic activity (EC 2.4.1.265)
      via loss-of-function and complementation. Core MF.
    supported_by:
      - reference_id: PMID:12480927
        supporting_text: "which catalyzes this reaction"
      - reference_id: PMID:12480927
        supporting_text: "suggesting inefficient addition of the second glucose residue onto"
- term:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:15235028
  qualifier: enables
  review:
    summary: >-
      Experimental (IMP) support for ALG8's glucosyltransferase activity from
      Schollen et al. 2004; UniProt records that the CDG1H variants T47P and
      G275D show "decreased dolichyl pyrophosphate Glc1Man9GlcNAc2
      alpha-1,3-glucosyltransferase activity", directly implicating ALG8 in this
      reaction. Core molecular function.
    action: ACCEPT
    reason: >-
      Variant characterization demonstrates reduced enzymatic activity, an
      experimental measure of the annotated MF; curator read full text.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "decreased dolichyl pyrophosphate\nFT                   Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity"
      - reference_id: PMID:15235028
        supporting_text: "(CDG-Ih) (ALG8 deficiency)"
- term:
    id: GO:0004583
    label: dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446189
  qualifier: enables
  review:
    summary: >-
      Reactome TAS to GO:0004583, the parent term for Dol-P-Glc-dependent
      alpha-glucosyltransferase activity. This is correct but less precise than
      the specific EC 2.4.1.265 term GO:0042283 that is already annotated
      experimentally. It captures the Dol-P-Glc donor specificity, which is
      biologically important.
    action: MODIFY
    reason: >-
      The essence (Dol-P-Glc-dependent alpha-glucosyltransferase) is correct but
      too general; the specific activity term GO:0042283 (the exact reaction
      ALG8 catalyzes) is preferable.
    proposed_replacement_terms:
      - id: GO:0042283
        label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
    supported_by:
      - reference_id: Reactome:R-HSA-446189
        supporting_text: "The second glucose (supplied from the donor dolichol-phosphate-glucose) is added to the N-glycan precursor, mediated by ALG8"
- term:
    id: GO:0004583
    label: dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4724330
  qualifier: enables
  review:
    summary: >-
      Reactome TAS (from the "Defective ALG8 causes CDG-1h" disease reaction) to
      the parent term GO:0004583. Same activity as the sibling Reactome
      annotation; correct but less precise than the specific EC 2.4.1.265 term.
    action: MODIFY
    reason: >-
      Correct Dol-P-Glc-dependent glucosyltransferase activity but too general;
      prefer the specific GO:0042283 term.
    proposed_replacement_terms:
      - id: GO:0042283
        label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
    supported_by:
      - reference_id: Reactome:R-HSA-4724330
        supporting_text: "normally adds the second glucose moiety to the lipid-linked oligosaccharide precursor (LLO aka N-glycan precursor) which is required for subsequent N-glycosylation of proteins"
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      ISS transfer (from mouse ortholog Q6P8H8) to protein N-linked
      glycosylation. Consistent with the experimental IMP and the IEA (Ensembl)
      annotations to the same term; ALG8 assembles the glycan precursor used in
      N-glycosylation. Correct.
    action: ACCEPT
    reason: >-
      Sequence-similarity inference to a well-supported process; redundant with
      but consistent with the human experimental annotation.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "the glycan precursors employed in\nCC       protein asparagine (N)-glycosylation"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4724330
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS ER membrane localization, consistent with the experimental
      and UniProt-curated ER membrane location. Correct and core.
    action: ACCEPT
    reason: >-
      Reproduces the well-supported ER membrane localization of this multi-pass
      membrane enzyme.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-446189
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS ER membrane localization (duplicate of the sibling Reactome
      CC annotation), consistent with experimental and UniProt evidence.
      Correct and core.
    action: ACCEPT
    reason: >-
      Reproduces the well-supported ER membrane localization; duplicates are
      acceptable across evidence sources.
    supported_by:
      - reference_id: file:human/ALG8/ALG8-uniprot.txt
        supporting_text: "SUBCELLULAR LOCATION: Endoplasmic reticulum membrane"
- term:
    id: GO:0006487
    label: protein N-linked glycosylation
  evidence_type: IMP
  original_reference_id: PMID:12480927
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) evidence that ALG8 deficiency (CDG-Ih) impairs protein
      N-linked glycosylation (Chantret et al. 2003), which defined this new
      subtype of type I congenital disorders of glycosylation — disorders caused
      by defective assembly of the dolichyl-linked oligosaccharide required for
      protein glycosylation. Correct.
    action: ACCEPT
    reason: >-
      Patient loss-of-function evidence links ALG8 to N-glycosylation via
      defective LLO assembly; consistent with other N-glycosylation annotations.
    supported_by:
      - reference_id: PMID:12480927
        supporting_text: "the underlying cause of this new CDG I"
      - reference_id: PMID:12480927
        supporting_text: "biosynthesis of the dolichyl-linked oligosaccharide"
references:
- id: file:human/ALG8/ALG8-uniprot.txt
  title: UniProtKB Q9BVK2 (ALG8_HUMAN)
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12480927
  title: A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase
    defines a new subtype of congenital disorders of glycosylation.
  findings: []
- id: PMID:15235028
  title: Clinical and molecular features of three patients with congenital disorders
    of glycosylation type Ih (CDG-Ih) (ALG8 deficiency).
  findings: []
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: Reactome:R-HSA-446189
  title: Addition of a second glucose to the N-glycan precursor by ALG8
  findings: []
- id: Reactome:R-HSA-446193
  title: Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide,
    LLO) and transfer to a nascent protein
  findings: []
- id: Reactome:R-HSA-4724330
  title: Defective ALG8 does not add glucose to the N-glycan precursor
  findings: []
core_functions:
- description: >-
    ER-lumenal, Dol-P-Glc-dependent alpha-1,3-glucosyltransferase (EC 2.4.1.265)
    that transfers the second glucose from dolichyl-phosphate-glucose onto
    Glc1Man9GlcNAc2-PP-dolichol to give Glc2Man9GlcNAc2-PP-dolichol during
    lipid-linked oligosaccharide (LLO) assembly.
  molecular_function:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  directly_involved_in:
    - id: GO:0006488
      label: dolichol-linked oligosaccharide biosynthetic process
  locations:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
    - id: GO:0098553
      label: lumenal side of endoplasmic reticulum membrane
  supported_by:
    - reference_id: file:human/ALG8/ALG8-uniprot.txt
      supporting_text: "adds the second glucose residue from dolichyl phosphate glucose"
    - reference_id: PMID:12480927
      supporting_text: "which catalyzes this reaction"
- description: >-
    Through assembly of the mature Glc3Man9GlcNAc2 lipid-linked oligosaccharide
    precursor that is transferred en bloc to nascent polypeptides, ALG8 is
    required for protein N-linked glycosylation; its loss causes CDG-Ih.
  molecular_function:
    id: GO:0042283
    label: dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity
  directly_involved_in:
    - id: GO:0006487
      label: protein N-linked glycosylation
  locations:
    - id: GO:0005789
      label: endoplasmic reticulum membrane
  supported_by:
    - reference_id: PMID:12480927
      supporting_text: "biosynthesis of the dolichyl-linked oligosaccharide"
    - reference_id: file:human/ALG8/ALG8-uniprot.txt
      supporting_text: "the glycan precursors employed in\nCC       protein asparagine (N)-glycosylation"